The ideal sedative agent for use in ICU probably does not exist. All sedative agents cause some degree of cardiovascular instability in critically ill patients. Longer-acting agents can be given by bolus, but may accumulate and do not allow rapid change in response to alterations in a patient’s condition. Shorter-acting agents are often preferred because they can be given by infusion, are less likely to accumulate and allow rapid change in depth, but they can be difficult to titrate.

In general single agents are not effective, either because they fail to achieve all the goals of sedation or because of unacceptable side-effects as the dose is increased. For this reason, it is more common to use a tailored combination of drugs. The principle employed is similar to that of ‘balanced anaesthesia’. By combining the benefits of more than one class of agent, satisfactory levels of sedation can be achieved at much lower doses than could be achieved using either agent alone, thus allowing some of the adverse effects of individual agents to be reduced. A typical combination is that of an opioid (e.g. fentanyl) together with a benzodiazepine (e.g. midazolam). This combination provides analgesia, sedation and anxiolysis. The advantages and disadvantages of these agents are shown in Table 3.1.

TABLE 3.1 Advantages and disadvantages of opioids and benzodiazepines for ICU sedation

The choice of agents will depend on local protocols and the clinical condition of the patient. If the balance of a patient’s problem is pain, then analgesia is the main requirement. Epidural anaesthesia, other regional anaesthetic techniques and patient-controlled analgesia (PCA) may be useful. (See Postoperative analgesia, p. 349.) If the balance of the patient’s problem is agitation, then the main requirement may be for sedative or anxiolytic agents. Haloperidol and other major tranquillizers are appropriate for the treatment of delirium and psychosis and recent guidelines have placed greater emphasis on the use of these agents (see Acute confusional states below). Tables 3.2 and 3.3 provide a guide to commonly used analgesic and sedative drugs.

TABLE 3.2 Commonly used analgesic agents

TABLE 3.3 Commonly used sedative agents (doses based on 70 kg adult)

Propofol is perhaps one of the most widely used sedative agents in adult ICU. Bolus doses of 1–3 mg / kg are sufficient to induce anaesthesia (e.g. prior to intubation). Smaller doses of 10–20 mg repeated to effect may be useful for increasing the depth of sedation, e.g. prior to suction or painful procedures.

There have been ongoing reports of inhaled anaesthetic agents being used for sedation in critical care. These may be of value in specific circumstances. Isoflurane and other volatile agents may be useful in asthma and severe bronchospasm because of their bronchodilator properties. Specific systems for delivering volatile agents into ventilator circuits on the ICU have been developed. Nitrous oxide may be of value for changes of burns dressings, but should not be used for more than 12 h because of bone marrow suppression.

Ideally patients should be awake, pain-free, able to move about as much as possible and be able to cooperate with physiotherapy and nursing care. Excessive sedation should be avoided. The potential problems associated with over-sedation include:

prolonged need for IPPV / intubation

haemodynamic instability

gastrointestinal tract stasis

potential immune suppression

potential organ toxicity

difficulty in assessing neurological state

increased withdrawal phenomena, delirium, hallucinations and nightmares in the post-critical illness period.

To avoid excessive sedation, agents should be titrated according to the balance of the patient’s needs. In practice, this can be difficult. The requirement for sedation differs markedly between patients. Younger, fitter patients generally require more sedative and analgesic drugs. Patients who abuse alcohol and other centrally acting drugs may be very difficult to sedate because of cross-tolerance between the abused substance and the prescribed sedative or analgesic agents. Relatives and patients may deny or conceal such abuse. Acute tolerance to drugs used for sedation in ICU may also occur.

In addition, the pharmacokinetics of many sedative drugs used in critical illness is poorly understood. Only limited information is available on drug metabolism and excretion in the critically ill. Drug trials performed in rats, healthy ‘volunteers’, ASA I patients and patients with compensated cirrhosis and uraemia are of little relevance to the critically ill ICU patient, in whom abnormalities in the distribution, metabolism and elimination of drugs are common. Regular reassessment of the need for, and level of, sedation is therefore required.

Sedation scoring systems may be useful in helping titrate levels of sedation. A typical score (performed hourly) together with appropriate responses is shown in Table 3.4.

TABLE 3.4 Sedation score

Where drugs are given by continuous infusion accumulation can occur and studies have consistently shown that patients tend to be over-sedated. Regular reassessment of sedation, and the use of sedation-free periods or ‘sedation holds’ can reduce the duration of tracheal intubation and ventilatory support. Many units now consider sedation holds on a daily basis. Typically sedation (not analgesia) is stopped once a day, to allow assessment. Ideally, sedation is held until the patient is able to follow commands.

Check that sedative infusions are running correctly and at the prescribed dose.

Exclude possible causes of agitation, including: full bladder, painful wounds, hypoxia, hypercarbia, and endotracheal tube touching carina.

Review other drug therapy and stop where appropriate. Many drugs (for example H₂ blockers) have the potential to induce confusional states.

Consider tracheostomy or nasal intubation. These are often better tolerated, and allow sedative and analgesic drugs to be significantly reduced.

Consider alternative sedative / analgesic agents if appropriate (e.g. paracetamol, NSAIDs, gabapentin, tricyclics). Seek advice.

Consider alternative analgesic techniques if appropriate (e.g. epidural or regional nerve blocks).

Eventually all patients need to be weaned off sedative agents. There is often a difficult phase during which the patient is partially sedated but unable to cooperate due to residual drug effects. Real problem patients (e.g. after head injury or suffering from withdrawal of drugs or alcohol), may be best nursed on a mattress on the floor. This reduces risk of harm should the patient fall out of bed. (See Withdrawal phenomena / acute confusional states below.)

If a patient fails to regain full consciousness after sedative and analgesic drugs have been stopped for a period of time, the question invariably arises as to ‘why?’ This may be due to the accumulation of drugs or their active metabolites, which resolves with time, but other causes of coma or ‘apparent coma’ should be excluded. Consider:

Effects of sepsis. Encephalopathy is common (for example as part of multiple organ failure).

Metabolic derangement / encephalopathy.

Seizure activity.

Structural brain damage (including CVA, hypoxic brain injury).

Awake patients who cannot respond (‘locked-in syndrome’).

Residual neuromuscular blockade (see p. 45).

Critical illness neuromyopathy (see p. 304).

Severe muscle weakness is common following critical illness so it may not be immediately apparent that the patient is actually awake, but unable to move. A similar clinical picture may also be seen in the presence of pontine lesions (e.g. following central pontine myelinolysis or brainstem stroke). Careful clinical examination is required to ascertain the true clinical picture. An EEG and CT scan may be helpful. If no other cause of coma can be established and failure to wake up is considered to result from the accumulation of sedative agents, a trial of naloxone or flumazenil may occasionally be diagnostic (Table 3.5). This is not without risk, however, and may precipitate convulsions. Seek senior advice.

TABLE 3.5 Naloxone and flumazenil

* Both drugs have a short half-life (approximately 20 min), leading to the risk of recurrence of respiratory depression and sedation. Side-effects include fits, hypertension, and dysrhythmias. Do not infuse over long periods of time. Ventilate the patient and await resolution as redistribution and metabolism of drugs occur!

When drugs used before admission, or sedative drugs given in ICU are stopped, drug withdrawal states may develop. This may result in seizures, hallucinations, delirium tremens, confusional states, agitation and aggression. Elderly patients are particularly susceptible. These phenomena are difficult to control without further heavy sedation, but usually settle over time. You should look for and treat any reversible causes of confusion (Box 3.1).

Drugs that can be useful for the control of acute confusional states, including those induced by the withdrawal of mixed sedative agents, are shown in Table 3.6. You should generally seek senior advice before resorting to these agents.

TABLE 3.6 Drugs for the treatment of acute confusional states

* Large number of actions and side-effects. Particularly beware of alpha blockade and hypotension. (Numerous newer antipsychotic agents, e.g. olanzapine, are now available. Seek advice.)